Advanced or Metastatic ER+ Breast Cancer
Conditions
Keywords
LSZ102, LEE011, ribociclib, Kisqali, BYL719, alpelisib, ER+ breast cancer, advanced ER+ breast cancer, metastatic ER+ breast cancer, SERD, SERM, fulvestrant, tamoxifen, aromatase inhibitor, ESR1, mtESR1, wtESR1, estrogen receptor, endocrine therapy
Brief summary
To characterize the safety and tolerability, identify recommended doses and regimens for future studies, pharmacokinetics (PK), pharmacodynamics (PD) and anti-tumor activity of LSZ102 as a single agent and in combination with either LEE011 or BYL719 in adult patients with locally advanced or metastatic ER+ breast cancer who have progressed after endocrine therapy.
Interventions
DRUGLSZ102
LSZ102
DRUGLEE011
LEE011
DRUGBYL719
BYL719
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent must be obtained prior to any procedures * Histologically and/or cytologically confirmed diagnosis of ER+/HER2- breast cancer * Advanced or metastatic breast cancer * Must be able to swallow tablets and capsules
Exclusion criteria
* Symptomatic CNS metastases * Patients whose laboratory values do not meet protocol criteria * Clinically significant cardiac disease * Impaired gastrointestinal function (GI) or GI disease that may significantly alter the absorption of oral medications Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose limiting toxicities (DLTs) | Day 1 - Day 28 of Cycle 1 (28 day cycle) | The dose escalation part of the study will be guided by well-established statistical methods/models to estimate the maximum tolerated doses (MTD)and/or recommended doses for expansion (RDE). Safety, pharmacokinetic and pharmacodynamics data will guide dose escalation decisions. |
| Safety and tolerability of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719 | Approximately 3 years | Incidence and severity of adverse events, serious adverse events, clinical laboratory values, vital signs, ECGs, dose interruptions, dose reductions and dose intensity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | 3 years | Assessment of preliminary anti-tumor activity of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719 |
| Disease control rate (DCR) | 3 years | Assessment of preliminary anti-tumor activity of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719 |
| Plasma concentration of study medications | 1 cycle (28 day cycle) | Plasma concentration versus time |
| Plasma concentration under fasted condition and fed condition | Up to 2 cycles (28 day cycle) | Plasma concentration versus time under fasted and fed conditions |
| Levels of Pharmacodynamic marker Estrogen receptor (ER) | 3 years | To assess pharmacodynamics effect |
| Overall response rate (ORR) | Approximately 3 years | Assessment of preliminary anti-tumor activity of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719. ORR is defined as the proportion of patients with a best overall response of complete response or partial response. |
| Levels of Pharmacodynamic marker pS6 | 3 years | To assess the pharmacodynamic effect |
| Pharmacokinetics (PK) parameter AUC | 6 cycles (28 day cycle) | AUC = Area under curve |
| PK parameter Cmax | 6 cycles (28 day cycle) | Cmax = Maximum observed plasma concentration after drug administration |
| PK parameter Tmax | 6 cycles (28 day cycle) | Tmax = Time to reach Cmax |
| PK parameter Cmin | 6 cycles (28 day cycle) | Cmin = Minimum observed plasma concentration after drug administration |
| Levels of Pharmacodynamic marker Progesterone receptor (PgR) | 3 years | To assess the pharmacodynamic effect |
| Duration of Response (DOR) | 3 years | Assessment of preliminary anti-tumor activity of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719 |
Countries
Belgium, France, Germany, Italy, Japan, Singapore, United States
Outcome results
None listed